Influence of OSMAC-Based Cultivation in Metabolome and Anticancer Activity of Fungi Associated with the Brown Alga Fucus vesiculosus

Abstract

The fungi associated with marine algae are prolific sources of metabolites with high chemical diversity and bioactivity. In this study, we investigated culture-dependent fungal communities associated with the Baltic seaweed Fucus vesiculosus. Altogether, 55 epiphytic and endophytic fungi were isolated and identified. Twenty-six strains were selected for a small-scale One-Strain-Many-Compounds (OSMAC)-based fermentation in four media under solid and liquid culture regimes. In total, 208 fungal EtOAc extracts were tested for anticancer activity and general cytotoxicity. Ten most active strains (i.e., 80 extracts) were analyzed for their metabolome by molecular networking (MN), in-silico MS/MS fragmentation analysis (ISDB–UNPD), and manual dereplication. Thirty-six metabolites belonging to 25 chemical families were putatively annotated. The MN clearly distinguished the impact of culture conditions in chemical inventory and anticancer activity of the fungal extracts that was often associated with general toxicity. The bioactivity data were further mapped into MN to seek metabolites exclusively expressed in the active extracts. This is the first report of cultivable fungi associated with the Baltic F. vesiculosus that combined an OSMAC and an integrated MN-based untargeted metabolomics approaches for efficient assessment and visualization of the impact of the culture conditions on chemical space and anticancer potential of the fungi.

Mining the Metabolome and the Agricultural and Pharmaceutical Potential of Sea Foam-Derived Fungi

“…With the exception of Plectosphaerella, all the other genera were also identified in a similar study, which showed the diversity in sea foam-derived fungi on the coast of the Canadian Prince Edward Island [4]. The literature shows that these species are common across a wide array of niches in both terrestrial and marine environments [43][44][45][46]. Similar to previous studies, the majority of sea foam fungal isolates found in this study are ubiquitous saprophytes [1,4].…”

Pyrenosetin D, a New Pentacyclic Decalinoyltetramic Acid Derivative from the Algicolous Fungus Pyrenochaetopsis sp. FVE-087

“…The endophytic fungus FVE-087 (GenBank accession number: MH881502) was isolated from the inner thallus of the brown alga Fucus vesiculosus collected at Kiel Fjord (Baltic Sea, Germany). The initial taxonomic study of FVE-087 revealed its taxonomical identity at order level, i.e., Pleosporales [22]. The re-amplification of ITS1-5.8S rRNA gene-ITS2 region yielded a longer 408 bp fragment, which enabled its identification at the genus level.…”

“…The fungal strain Pyrenochaetopsis sp. FVE-087 (GenBank accession number: MH881502) was obtained from Fucus vesiculosus specimens that were collected in Falckenstein Beach (54 • 23 22.6 N, 10 • 11 26.4 E), Kiel Fjord, Baltic Sea, in December 2015, Germany [22]. The fungus was identified by morphological observation, analysis of the ITS1-5.8S rRNA gene-ITS2 region and by building a phylogenetic tree with 14 related strains including the Pyrenochaetopsis sp.…”

“…As part of our on-going project aiming to investigate the cultivable mycobiome of seaweeds, we have previously isolated 55 epiphytic and endophytic fungi from the Baltic brown alga Fucus vesiculosus [22]. In-depth chemical investigation of the endophytic fungus Pyrenochaetopsis sp.…”

“…FVE-087 attracted our attention. In preliminary screenings, the crude extract of this strain also exerted potent anticancer activity [22]. Chemical work-up of this endophyte monitored by anticancer activity against the same melanoma cell line (A-375) resulted in the purification of a new pentacyclic decalinoyltetramic acid derivative, pyrenosetin D (1), along with two known decalins wakodecaline A (2) and wakodecaline B (3).…”